LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

Mura, M. et al. (2015) LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene, 34(39), pp. 5025-5036. (doi: 10.1038/onc.2014.428) (PMID:25531318) (PMCID:PMC4430325)

Abstract

RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5′-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Mura, M., Hopkins, T. G., Michael, T., Abd-Latip, N., Weir, J., Aboagye, E., Mauri, F., Jameson, C., Sturge, J., Gabra, H., Bushell, M., Willis, A. E., Curry, E., and Blagden, S. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncogene
• Publisher: Nature Publishing Group
• ISSN: 0950-9232
• ISSN (Online): 1476-5594
• Published Online: 22 December 2014
• Copyright Holders: Copyright © 2015 Macmillan Publishers Limited
• First Published: First published in Oncogene 34(39): 5025-5036
• Publisher Policy: Reproduced under a Creative Commons License